The objective of this proposal is to determine the cellular basis for changes in pituitary responsiveness to gonadotropin releasing hormone in the normal aging rat. The anterior pituitary produces hormones which, in turn, regulate major physiological functions including reproduction, carbohydrate and salt metabolism, and growth. A body of information suggests that changes in these functions during senescence is correlated with changes in pituitary responsiveness to hypothalamic releasing hormone. The present study has been designed to quantitate the contribution of specific changes which result in this altered pituitary responsiveness to gonadotropin releasing hormone. An understanding of these functions will be particularly useful since it will explain the basis for physiological changes in gonadotropin levels and biological activity. It is probable that altered responsiveness is mediated through either molecular changes in GnRH receptor levels, changes in coupling of the receptor to mechanism of stimulation, or changes in gonadotropin processing and secretion. Analysis of these individual steps in normal aging rats will result in the development of a cellular model for altered pituitary responsiveness.